Methylglyoxal/Glyoxalase-1/Glutathione Biomarker Panel for Long COVID

Background: Long COVID (LC) affects millions worldwide, causing diverse symptoms, from fatigue, dyspnea, and cough to multiorgan complications. Immune activation, endothelial dysfunction, hypoxia, and metabolic dysregulation are implicated, although mechanisms remain unclear. This study aimed to identify a biomarker panel linking endothelial dysfunction, hypoxia, and metabolic shifting to diverse LC symptoms. Methods: Plasma biomarkers were compared between 30 individuals with LC and 30 controls. Glucotoxic methylglyoxal, glyoxalase-1 and glutathione, indicators of methylglyoxal detoxification, soluble VAP-1 (sVAP-1, SSAO), TNF-α, and IL-1β were assessed. STRING and molecular docking explored protein associations and potential MG–Glo-1 interactions. Results: Compared with controls, individuals with LC exhibited approximately 200% higher MG, 20% lower glyoxalase-1, 45% lower glutathione, and 50% higher SSAO activity. TNF-α and IL-1 increased 165% and 145%, respectively. Symptom numbers correlated with methylglyoxal (r = 0.65) and inversely with Glo-1 (r = −0.61) and GSH (r = −0.47), but not SSAO, TNF-α, or IL-1β. Methylglyoxal was inversely correlated with glyoxalase-1 (r = −0.59) and GSH (r = −0.67), but not SSAO, TNF-α, or IL-1β. STRING analysis predicted associations involving glyoxalase-1, VAP-1, and other proteins, while docking suggested MG interaction with glyoxalase-1(−4.82 kcal/mol). Conclusion: MG/Glo-1/glutathione represents a novel biomarker panel for diverse LC symptoms.